Given the ubiquitous nature of K+ channels, it seems likely that these channels play important roles in the normal function of all cells. Thus, it is important to determine the purpose of individual channels in specific cells and tissues of the body. As a step toward this goal, I plan to generate a null mutant ('knock-out') mouse that lacks the Kv1.3 (n type), voltage-gated K+channel. This will be done using techniques, such as homologous recombination that are already available and that have previously been used in this laboratory to make a Kv3.1 (l type) K+ channel-deficient mouse. The ultimate goal is to determine the phenotype of Kv1.3-deficient mice using behavioral, morphologic, physiologic and immunologic techniques. Although little is currently known about the location or the role of the Kv1.3 channel in animals, it has been identified as the n type channel found in various cells of the human and mouse immune systems, including T lymphocytes. Previous studies of the Kv1.3 channel in T lymphocytes led to the interesting suggestion that it is involved in mitogen-induced activation of T cells. Some evidence of its expression in the brain has also been found. Thus, my initial studies of the mutant mice will focus on the immune and nervous systems. I expect to gain information regarding the role of the Kv1.3 K+ channel in the development and function of these systems. Information regarding a role of this channel in disease may also be derived from this study.